Curcumin nanocrystals mitigate hypoxia-induced cardiac injury through redox regulation and CHOP-CytC-caspase pathway...

Secondary cardiac injury is a critical complication following traumatic insults under hypoxic plateau conditions. This study investigated whether curcumin nanocrystals protect against hypoxic trauma-induced myocardial injury and explored the underlying mechanisms. A piglet model of abdominal firearm injury under simulated high-altitude conditions was established, and animals received intravenous curcumin nanocrystals after injury. Myocardial injury, apoptosis, oxidative stress, inflammation, and apoptotic signaling pathways were evaluated using histopathology, biochemical assays, TUNEL staining, ELISA, and Western blotting. Hypoxic trauma markedly aggravated myocardial damage, as indicated by increased H&E injury scores (8.8 ± 0.7 in AIG 8 h vs. 3.2 ± 0.4 in PIG 8 h), elevated serum CK (2433 ± 125 vs. 1754 ± 117 ng/mL) and CK-MB (608 ± 25 vs. 510 ± 24 ng/mL), and a higher apoptotic rate (10.0 ± 1.2% vs. 1.5 ± 1.0%). Curcumin nanocrystal treatment significantly reduced myocardial injury scores (4.9 ± 0.5), apoptosis (3.6 ± 2.5%), and tissue ROS levels (18% reduction), and attenuated IL-1β, IL-6, and TNF-α expression. Mechanistically, curcumin nanocrystals decreased CHOP (23.3%), CytC (21.4%), caspase-9 (15.6%), and caspase-3 (14.3%) expression, while partially restoring Bcl-2 levels, indicating inhibition of ERS-driven mitochondrial apoptosis via the CHOP/CytC/caspase axis (all p < 0.05). Given their improved solubility and bioavailability, intravenous curcumin nanocrystals may represent a feasible therapeutic approach for acute trauma care at high altitude. Limitations include the short observation period, lack of long-term cardiac functional assessment, and potential species differences. Nevertheless, these findings highlight the therapeutic potential of curcumin nanocrystals for preventing secondary cardiac injury in hypoxic trauma.